title: Embryonic nervous system genes predominate in searches for dinucleotide simple sequence repeats flanked by conserved sequences.
abstract: To study evolution of dinucleotide simple sequence repeats (diSSRs) we searched recently available mammalian genomes for UTR-localized diSSRs with conserved upstream flanking sequences (CFS). There were 252 reported Homo sapiens genes containing the repeats (AC)n, (GT)n, (AG)n or (CT)n in their UTRs including 22 (8.7%) with diSSR-upstream flanking sequences conserved comparing divergent mammalian lineages represented by Homo sapiens and the marsupial, Monodelphis domestica. Of these 22 genes, 19 had known functions including 18 (95%) that proved critical for mammalian nervous systems (Fishers exact test, P<0.0001). The remaining gene, Cd2ap, proved critical for development of kidney podocytes, cells that have multiple similarities to neurons. Gene functions included voltage and chloride channels, synapse-associated proteins, neurotransmitter receptors, axon and dendrite pathfinders, a NeuroD potentiator and other neuronal activities. Repeat length polymorphism was confirmed for 68% of CFS diSSRs even though these repeats were nestled among highly conserved sequences. This finding supports a hypothesis that SSR polymorphism has functional implications. A parallel study was performed on the self-complementary diSSRs (AT)n and (GC)n. When flanked by conserved sequences, the self-complementary diSSR (AT)n was also associated with genes expressed in the developing nervous system. Our findings implicate functional roles for diSSRs in nervous system development.
authors.affiliation: Department of Urology, University of Washington, Seattle, WA 98195, USA. dri@u.washington.edu
authors.forename: Donald E
authors.initials: DE
authors.lastname: Riley
authors.forename: John N
authors.initials: JN
authors.lastname: Krieger
mesh_terms: D000818:Animals; D001482:Base Composition / Q000235:genetics; D001483:Base Sequence; D017124:Conserved Sequence / Q000235:genetics*; D021901:DNA, Intergenic / Q000235:genetics*; D018900:Dinucleotide Repeats / Q000235:genetics*; D050437:Genes, Developmental; D006801:Humans; D051379:Mice; D018598:Minisatellite Repeats / Q000235:genetics*; D009420:Nervous System / Q000196:embryology* / Q000378:metabolism*; D016366:Open Reading Frames / Q000235:genetics; D011110:Polymorphism, Genetic
chemical_list: D021901:DNA, Intergenic